Serotonin (5-hydroxytryptamine, 5-HT) is acknowledged as a major neuromodulator of nervous systems in both invertebrates and vertebrates. It has been proposed for several decades that it impacts animal cognition and behavior. In spite of a completely distinct organization of the 5-HT systems across the animal kingdom, several lines of evidence suggest that the influences of 5-HT on behavior and cognition are evolutionary conserved. In this review, we have selected some behaviors classically evoked when addressing the roles of 5-HT on nervous system functions. In particular, we focus on the motor activity, arousal, sleep and circadian rhythm, feeding, social interactions and aggressiveness, anxiety, mood, learning and memory, or impulsive/compulsive dimension and behavioral flexibility. The roles of 5-HT, illustrated in both invertebrates and vertebrates, show that it is more able to potentiate or mitigate the neuronal responses necessary for the fine-tuning of most behaviors, rather than to trigger or halt a specific behavior. 5-HT is, therefore, the prototypical neuromodulator fundamentally involved in the adaptation of all organisms across the animal kingdom.

The crayfish that was afraid of the dark: We tend to assume that complex emotions, such as anxiety, only occur in mammals or other cognitively complex vertebrates. But a heightened sense of awareness and the avoidance of novel or dangerous environments could be helpful for any animal species. Fossat et al. show that crayfish exposed to a stressful electric field refuse to enter dark arms in a light/dark maze, even after the electric field has been removed. The animals calmed down when they were injected with an anxiolytic drug used to treat anxiety in humans, and they entered the dark as normal. The stressed animals had increased levels of the neurotransmitter serotonin in the brain, and injections of serotonin induced anxiety-like behavior in control animals. Thus, these invertebrates display a primitive form of anxiety that shares a mechanism with the more complex emotions displayed by vertebrates. Science , this issue p. 1293

In the animal kingdom, biogenic amines are widespread modulators of nervous system that frequently interact in the control of mood. Our previous investigations in crayfish (Procambarus clarkii) have established that stress induces changes in brain serotonin (5-HT) concentrations that are responsible for the appearance of anxiety-like behavior (ALB). The following study further analyzes the roles of 5-HT and of another biogenic amine, dopamine (DA), on crayfish response to stress. Results showed that the intensity of crayfish ALB depended on the intensity of stressful stimulation and was associated with increased concentrations of 5-HT in the brain. These 5-HT levels were significantly correlated, before, as well as after stress, with those of DA, which were approximately 3-5 times less abundant. However, whereas ALB intensity was clearly correlated with brain 5-HT concentrations, it was not significantly correlated with those of DA. Moreover, contrary to 5-HT, DA injections were not able to elicit stress response and ALB. Incidentally, 5-HT and DA levels were not modified by treatment with the anxiolytic chlordiazepoxide, confirming that ALB suppression by this ligand of GABA-A receptors acted downstream and independently from changes in crayfish bioamine levels. Our study also provided evidence that the anxiogenic effect of 5-HT injections can be prevented by a preliminary injection of 5-HT antagonists. Altogether, our results emphasize that the rises in the brain concentrations of 5-HT, but not of DA, play a role in controlling the induction and the intensity of crayfish ALB.

Social interactions leading to dominance hierarchies often elicit psychological disorders in mammals including harassment and anxiety. Here, we demonstrate that this sequence also occurs in an invertebrate, the crayfish Procambarus clarkii. When placed in the restricted space of an aquarium, crayfish dyads generally fight until one of the opponents suddenly escapes, thereafter clearly expressing a submissive behaviour. Nevertheless, the winner frequently keeps on displaying excessive aggressive acts, having deleterious consequences in losers and interpreted as harassment behaviour. We indeed observed that, contrary to winners, losers expressed anxiety-like behaviour (ALB) in correlation with the stress intensity they suffered during the harassment period mainly. Injections of an anxiolytic abolished ALB, confirming its homology with anxiety. A serotonin (5-HT) antagonist had the same effect, suggesting a role for 5-HT, whose brain concentrations increased much more in losers than in winners. Our findings suggest that the bases of harassment and of its anxiogenic consequences have emerged very early during evolution, and emphasize crayfish as an unexpected but potentially fruitful model for the study of these social disorders.

In larval xenopus, locomotor-induced oculomotor behavior produces gaze-stabilizing eye movements to counteract the disruptive effects of tail undulation during swimming. While neuronal circuitries responsible for feed-forward intrinsic spino-extraocular signaling have recently been described, the resulting oculomotor behavior remains poorly understood. Conveying locomotor CPG efference copy, the spino-extraocular motor command coordinates the multi-segmental rostrocaudal spinal rhythmic activity with the extraocular motor activity. By recording sequences of xenopus tadpole free swimming, we quantified the temporal calibration of conjugate eye movements originating from spino-extraocular motor coupled activity during pre-metamorphic tail-based undulatory swimming. Our results show that eye movements are produced only during robust propulsive forward swimming activity and increase with the amplitude of tail movements. The use of larval isolated in vitro and semi-intact fixed head preparations revealed that spinal locomotor networks driving the rostral portion of the tail set the precise timing of the spino-extraocular motor coupling by adjusting the phase relationship between spinal segment and extraocular rhythmic activity with the swimming frequency. The resulting spinal-evoked oculomotor behavior produced conjugated eye movements that were in phase opposition with the mid-caudal part of the tail. This time adjustment is independent of locomotor activity in the more caudal spinal parts of the tail. Altogether our findings demonstrate that locomotor feed-forward spino-extraocular signaling produce conjugate eye movements that compensate specifically the undulation of the mid-caudal tail during active swimming. Finally, this study constitutes the first extensive behavioral quantification of spino-extraocular motor coupling, which sets the basis for understanding the mechanisms of locomotor-induced oculomotor behavior in larval frog.

Neuromechanical simulation was used to determine whether proposed thoracic circuit mechanisms for the control of leg elevation and depression in crayfish could account for the responses of an experimental hybrid neuromechanical preparation when the proprioceptive feedback loop was open and closed. The hybrid neuromechanical preparation consisted of a computational model of the fifth crayfish leg driven in real time by the experimentally recorded activity of the levator and depressor (Lev/Dep) nerves of an in vitro preparation of the crayfish thoracic nerve cord. Up and down movements of the model leg evoked by motor nerve activity released and stretched the model coxobasal chordotonal organ (CBCO); variations in the CBCO length were used to drive identical variations in the length of the live CBCO in the in vitro preparation. CBCO afferent responses provided proprioceptive feedback to affect the thoracic motor output. Experiments performed with this hybrid neuromechanical preparation were simulated with a neuromechanical model in which a computational circuit model represented the relevant thoracic circuitry. Model simulations were able to reproduce the hybrid neuromechanical experimental results to show that proposed circuit mechanisms with sensory feedback could account for resistance reflexes displayed in the quiescent state and for reflex reversal and spontaneous Lev/Dep bursting seen in the active state.